Compounds which have the property of inhibiting the action of metalloproteinases involved in connective tissue breakdown such as collagenases, stromelysins and/or gelatinases (known as "matrix metalloproteinases", and herein referred to as MMPs) are thought to be potentially useful for the treatment or prophylaxis of conditions involving such tissue breakdown, for example rheumatoid arthritis, osteoarthritis, osteopenias such as osteoporosis, periodontitis, gingivitis, corneal epidermal or gastric ulceration, and tumour metastasis, invasion and growth. MMP inhibitors are also of potential value in the treatment of neuroinflammatory disorders, including those involving myelin degradation, for example multiple sclerosis, as well as in the management of angiogenesis dependent diseases, which include arthritic conditions and solid tumour growth as well as psoriasis, proliferative retinopathies, neovascular glaucoma, ocular tumours, angiofibromas and hemangiomas. However, the relative contributions of individual MMPs in any of the above disease states is not yet fully understood.
Metalloproteinases are characterised by the presence in the structure of a zinc(II) ionic site. It is now known that there exists a range of metalloproteinase enzymes that includes human fibroblast collagenase (MMP-1), human neutrophil collagenase (MMP-8) and collagenase-3 (MMP-13), 72 kDa-gelatinase, 92 kDa-gelatinase, stromelysin-1, stromelysin-2 and PUMP-1 (J. F. Woessner, FASEB J, 1991, 5, 2145-2154).
Known classes of collagenase inhibitors include those disclosed in EP-A-0574758 (Roche), EP-A-0684240 (Roche), and WO 95/33731 (Roche). In general, the compounds disclosed in those publications may be represented by the structural formula (IA) ##STR2## in which X, Y and the N-containing ring are variable in accordance with the specific disclosures of the publications.